Effect of post-treatment with granulocyte colony-stimulating factor on endotoxin-induced lung injury in sheep.
We administered a bolus of G-CSF (250 micrograms/body) just after the infusion of endotoxin (1 microgram/kg) in awake sheep with chronic lung lymph fistula to examine the effect of post-treatment with G-CSF on endotoxin-induced lung injury. We measured pulmonary hemodynamics, lung lymph flow, and concentrations of thromboxane B2 and 6-keto-prostaglandin F1 alpha in plasma and lung lymph. In the G-CSF post-treated group, the pulmonary arterial pressure, pulmonary vascular resistance, and lung lymph flow did not significantly increase in the late period (3-5 h after endotoxin infusion). The arterial oxygen gas tension in the late period was higher in the G-CSF post-treated sheep than in those that received only endotoxin. Although the level of thromboxane B2 in plasma significantly increased at 1 h after endotoxin, the lung lymph flow did not increase much in the G-CSF post-treated group. We conclude that post-treatment with G-CSF instead attenuates the degree of pulmonary vascular leakage on endotoxin-induced lung injury and increased thromboxane B2, the principle metabolite of thromboxane A2, may not exacerbate the injury in awake sheep.
Hanaoka
M
M
First Department of Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
Kubo
K
K
Miyahara
T
T
Hayano
T
T
Koizumi
T
T
Kobayashi
T
T
Sekiguchi
M
M
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood / Q000378:metabolism; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology; D002245:Carbon Dioxide / Q000097:blood; D002908:Chronic Disease; D004731:Endotoxins / Q000633:toxicity*; D005402:Fistula / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D007958:Leukocyte Count / Q000187:drug effects; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects; D008171:Lung Diseases / Q000139:chemically induced* / Q000188:drug therapy*; D008196:Lymph / Q000378:metabolism / Q000502:physiology; D008206:Lymphatic Diseases / Q000188:drug therapy* / Q000503:physiopathology; D010100:Oxygen / Q000097:blood; D011652:Pulmonary Circulation / Q000502:physiology; D012756:Sheep; D013929:Thromboxane B2 / Q000097:blood / Q000378:metabolism
D004731:Endotoxins; D002245:Carbon Dioxide; D016179:Granulocyte Colony-Stimulating Factor; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; C044101:endotoxin, Escherichia coli; D010100:Oxygen